Producing a topical solution composition

ABSTRACT

The appearance of hyperpigmented lesions on human skin are reduced by applying a topical solution composition that includes a concentrated amount of resveratrol that has been extracted from red wine and is at a pH of between 2.5 and 5.5.

This present application is a Continuation Application of U.S.application Ser. No. 16/997,121, filed on Aug. 19, 2020 (now allowed),which is a Continuation Application of U.S. application Ser. No.15/715,037, filed on Sep. 25, 2017 (now U.S. Pat. No. 10,888,515), whichis a Continuation-in-Part of U.S. application Ser. No. 15/685,687, filedon Aug. 24, 2017 (abandoned), which is a Continuation Application ofU.S. application Ser. No. 11/837,735, filed on Aug. 13, 2007 (now U.S.Pat. No. 9,770,480), the entirety of which is incorporated herein byreference and made a part of the present disclosure.

TECHNICAL FIELD

The present invention is generally related to a topical solutioncomposition that revitalizes layers of the skin.

SUMMARY

The primary objective of the present invention is to produce a skintopical solution composition that revitalizes damaged skin. Theproduction of the topical solution is accomplished by providing a grapeextract and adding vitamins that are capable of increasing the pH and anaqueous solution with a carbomer base where the carbomer base acts as anemulsion stabilizer and where the grape extract is subjected to afermentation and mixing process that yields the highest conversion ofcis- and trans-piceid (a glucoside-analog of resveratrol) into cis- andtrans-resveratrol.

The topical solution comprises a number of ingredients depending on ifthe desired final form of the topical solution is a gel or a cream. At aminimum the ingredients for the topical solution must include a grapeextract, vitamins that are capable of increasing the pH and an aqueoussolution with a carbomer base where the carbomer acts as an emulsionstabilizer and where the grape extract is subjected to a fermentationand mixing process that yields the highest conversion of cis- andtrans-piceid (a glucoside-analog of resveratrol) into cis- andtrans-resveratrol.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 Image of subject before and after using the skin lotion.

FIG. 2 Image of subject before and after using the skin lotion.

FIG. 3 is a simplified process flow diagram for developing a topicalsolution.

FIG. 4A is a photograph of the face of patient #1 on day 1 of theexperiment described in Example 1, prior to any application of thetopical solution composition, where lesions are visibly apparent onpatient #1.

FIG. 4B is a photograph of the face of patient #1 on day 30 of theexperiment described in Example 1, after the final application of thetopical solution composition, where the number and/or size of thelesions that are visibly apparent on patient #1 have been reducedrelative to FIG. 4A.

FIG. 5A is a photograph of the face of patient #2 on day 1 of theexperiment described in Example 1, prior to any application of thetopical solution composition, where lesions are visibly apparent onpatient #2.

FIG. 5B is a photograph of the face of patient #2 on day 30 of theexperiment described in Example 1, after the final application of thetopical solution composition, where the number and/or size of thelesions that are visibly apparent on patient #2 have been reducedrelative to FIG. 5A.

BACKGROUND

The present invention relates to revitalizing layers of the skin whichhave been damaged by the environment. More specifically, sunlightexposure and particularly ultraviolet radiation can cause a variety ofskin changes and damages such as premature aging, and skin cancer. Thereare three main types of UV radiation, UVA, UVB, and UVC. UVC has theshortest wavelength. UVA on the other hand has the longest wavelength.However, as with any electromagnetic energy, the shortest wavelength isthe most susceptible to obstruction while the longest wavelength is theleast. UVC for example is almost completely blocked by the ozone layerin our atmosphere, while UVB penetrates the atmosphere relativelyunobstructed and causes damage in the outer layer of the skin. UVB,however, does not penetrate glass. UVA, on the other hand, can penetrateglass and deeper into the skin to cause skin damage.

On a cellular level, UV radiation can cause collagen breakdown, creationof free radicals, interfere with DNA repair, and suppress the immunesystem's ability to survey and destroy cancerous cells. Of thesedamaging effects, perhaps the most significant is the creation of freeradicals.

Oxygen molecules normally exist in stably bonded pairs. Free radicalsare created when ionizing energy like UV radiation strikes a stable,paired oxygen molecule splitting its paired electron bonding, resultingin two single oxygen molecules. These two oxygen molecules each have oneunpaired valence electron that is very reactive inside human tissues andcells. These free radical oxygen molecules react with organic moleculesin the connective tissue and cells stealing electrons away fromstructures that require those electrons for stable bonds. This causesdamage to enzymes, DNA's, collagen structures and cell wall stabilityand permeability. Damage to these cellular structures can cause forexample. DNA mutations (that lead to cancerous behavior); suppression ofenzymatic functions that regulate cellular signaling, apoptosis, immunefunctions, as well as, DNA repair.

One well known skin condition that occurs as a result of prolonged,cumulative effect of sun exposure is Actinic Keratosis, (AK's). AK's areby far the most common skin lesion with malignant potential on the skin.These lesions develop in a stepwise progression from subclinical skinchanges to overt, invasive Squamous Cell Carcinoma, (SCC). If leftuntreated, these AK lesions have 1 per 1000 per year chance of becomingcancerous.

Clinically, AK's present with a range of characteristics. They can bebarely perceptible to rough, elevated hyperkeratotic plagues severalcentimeters in diameter. The base may be light or dark, tan, pink, red,or a combination of these. Most typically though, they appear asmultiple discrete lesions that are small crusty, scaly or crumbly bumpor horn on an erythematous base.

Histologically, AK's share features with SCC. The histologicalcharacteristics are as follows: AK's are located in the epidermis andshow hyperkeratosis with intermittent large parakeratotic nuclei andoccasional mitotic figures; keratinocyte atypia along the basal layerspongiosis in the immediate suprabasalar layer; budding of the basallayer keratinocytes into the dermis; perivascular inflammation and solarelastosis.

Treatment of AK's typically consists of surgical destruction. Thedifficulty with surgical destruction is that it is difficult andimpractical to treat a large area of the skin that has large number oflesions.

Hyperpigmentation is the condition of the appearance of excessivepigmented lesions on skin, which are often considered unsightly andundesirable. The causes of hyperpigmentation can vary but includeexcessive exposure to UVA and UVB radiation, detrimental environmentalstress on skin through extended exposure, the side effects oflight-based medical therapies on skin via laser or other devices (whichis known as PIH or “Post-Inflammatory Hyperpigmentation”), hormonalchanges to the human body that occur during or after pregnancy, as wellas conditions such as melasma where pigmentation is a known side effect,or other physiological changes to the human body that can exhibithyperpigmentation as a reaction to stress or inability to processtoxicity within the body.

Historically hyperpigmentation has been one of the most difficult skinconditions to treat cosmetically, with traditional methods focusing onphysical reduction of the pigment at the outermost layer of the skin(the stratum corneum) via a manual or chemical exfoliation process. Theapplication of hydroquinone, a synthetic chemical originally compoundedas a means of developing photographs, as a topically-applied medicine toreduce hyperpigmentation became a widely used method since the 1970s.However, hydroquinone has been found to have potentially significanteffects if applied for too long of a period of time or if applied inhigher concentrations. Specifically, there have been many documentedcases of ocrhnosis where hyperpigmention is known to appear as areaction to high does of hydroquinone and becomes intractable withinskin. Because of safety considerations the health agencies of manynations have severely restricted or banned hydroquinone from usealtogether, or at a minimum eliminated it as an OTC or “over thecounter” medicine.

As a result, there is a need for a safer yet still effective means ofreducing hyperpigmention through topical means. There have been severalalternative compounds, both synthetic and from a botanical source, thathave been applied to reduce hyperpigmentation, such as Vitamin C orKojic Acid. However, these methods often have drawbacks in terms ofdifficulty to chemically stabilize, and have undesirable side effects onskin when applied.

DETAIL DESCRIPTION

The use of the present invention which, was further proven in studiesperformed by an independent research investigator at the Palo AltoMedical Foundation, greatly improves or completely resolves AK lesions.Furthermore, since the present invention consists of a topical solutionthat is topically applied it is not limited to impracticalities oftreating large areas of the skin like surgical destruction.

Recently there has been significant interest in the medical and healthindustry generated about red wine. Red wine is known to have severalbiologically active compounds; most of them belong to a family known aspolyphenols. Polyphenols are of great interest to the medical and healthindustry because of the potential benefits to human health. Thesecompounds possess antioxidant, anti-inflammatory, and anticarcinogenicproperties that are the focus of many current research investigations.

Polyphenols are a group of heterogeneous compounds with four mainclasses: flavonols, stilbenes, flavones, and phenolic acids. Suchcompounds include, for example, proanthocyanidins, quercitin,anthocyanins, and resveratrol and its glucoside analogs). Studiesinvolving these four main classes suggest that of the polyphenols,resveratrol may the most effective in anticancer property.

Resveratrol exist as a cis-isomer and a trans-isomer. It falls under aclass of polyphenols known as stilbenes. A glucoside analog ofresveratrol is found naturally, to varying levels, in the skin of grapesin its isomeric forms called cis- and trans-piceid.

In the past, it was not known how to produce a grape extract to includein a topical solution where the grape extract was not damaged in theproduction process. Also, it was not known how to produce a grapeextract that yields high levels of resveratrol. Finally due to fact thatred wine and red wine's extract naturally has an extremely low pH(between 1.0 and 2.0) it was not known how to produce a topical solutionthat would not inflame or burn the skin.

In the present invention the grape extract is mixed by using a coldprocess which does not damage the grape extract, parameters in thefermentation process are heavily controlled to maintain a specific ragethat yields high levels of resveratrol and certain ingredients are usedin the production process that increases the natural pH level of redwine thereby allowing one to produce a topical solution with anacceptable pH and with the highest quantity of active polyphenols.

The topical solution composition of the present invention includes agrape extract which is produced predominantly from grapes that are richin magenta color. We have found that grapes that are rich in magentacolor yield the highest amount of resveratrol due to the high tannincontent of the grapes' skin. We have also found that certain vintageslike Merlot and Cabernet yield the highest form of resteratrol contentbecause their vintage process includes more parts of the grapes' skin.Furthermore, there is a well known method of testing, growing andproducing grapes with high levels of resveratrol.

The process for developing the topical solution is referenced in theflow chart within FIG. 3 which starts with the harvesting stage (10)where grapes are harvested for their rich magenta color. The grapes arethen subjected to a fermentation process named in FIG. 3 as thefermentation stage (20) which is a process in which an agent causes anorganic substance to break down into simpler substances. Thefermentation process used to produce the grape extract in the presentinvention includes the addition of yeast as the agent which causes theanaerobic breakdown of the sugar within the grape extract into alcohol.It is important that the fermentation parameters are strictly enforced.Too much fermentation yields an alcohol level that is more than twopercent by volume. The increased level of alcohol above two percent byvolume is a result that occurs when the fermentation process has begunto break down the Coumaroyl CoA molecule thereby not allowing it toyield the best reaction thereby yielding a long chain molecule. Thepreferred length of fermentation for the present invention depends onthe temperature and humidity and the preferred range is between sevendays at a temperature of ninety five degrees Fahrenheit and 80 percenthumidity to forty five at a temperature of thirty five degreesFahrenheit and 30 percent humidity. This range yields the highestconversion of cis- and trans-piceid (a glucoside-analog of resveratrol)into cis-and trans-resveratrol without oxidizing the polyphenols. Afterthe fermentation process the grapes are then subjected to an extractionprocess which is performed in the extraction stage (30), where the waterand ethanol content produced during the fermentation process is slowlyremoved leaving only the constituents of the grapes behind in a stablepowder form.

This powder form of the grape extract is then subjected to the mixingstage (40) where depending if the designed outcome of the topicalsolution is a gel or cream various ingredients are added. The mixingprocess is particularly inventive due to the cold process mixing methodsemployed to mix the powder form of the grape extract into an aqueoussolution with a carbomer base. Additional ingredients are then furtheradded and mixed to increase the level of pH. The traditional mixingprocess uses heat to melt the ingredients thereby allowing theingredients to adequately mix together. It is well known in the art ofproducing skin lotions to use high temperatures between 100 and 300degrees Celsius in order to facilitate the melting and mixing of theingredients. We have found that the use of high temperatures causesheat-oxidation in the grape extract. Heat oxidation occurs when elevatedtemperatures increase the activity of oxygen and serves as a catalyst byexothermic reactions for the formation of Radical Oxygen Species (ROS)from oxygen. When anti-oxidants such as resveratrol are exposed toheat-oxidation they bind with the ROS thereby decreasing the amount ofresveratrol. In effect, heat-oxidization prematurely reduces oreliminates the anti-oxidant benefits of the grape extract.

In the present invention the mixing process of the grape extract isperformed in room temperature between twenty to forty degrees Celsiusthereby reducing any oxidation of the polyphenols caused by heat. Thislow temperature mixing process uses ingredients that are capable ofbeing mixed without the need for increased temperatures.

This limits the types of ingredients one can use to in a skin lotion. Wefound that the following ingredients and their percentages are mostcontusive to mixing by use of a cold process when producing a topicalsolution using the present invention where the topical solution is inthe form of a gel:

Gel Ingredients: Percentage D.I. Water 68.10 RedWine Extract 5.00 AloeBarbensis Extract 4.00 Cucumber Extract 3.00 Hylauronie Acid 2.50Isoplene Glycol 2.00 Tocopherol Acetate 2.00 Chamomile Extract 2.00Jojoba Oil 2.00 Hydrolyzed Milk Protein 2.00 Nettle (Urtica Diolica)Extract 0.50 Hydrolyzed Wheat Protein 0.50 Phytic Acid 0.50 Wheat GermOil 0.50 Horsetail Extract 0.50 Centella Assistica Extract 0.50Chlorella Vulgaris Extract 0.50 Hydrolyzed Algin 0.50 Butylene Glycol0.50 Naicinamide 0.50 Adensosine Triphosphate 0.50 D-Panthenol (VitaminB5) 0.50 Carbomer 0.20 Xanthan Gum 0.20 Methylparaben 0.20 Butylparaben0.20 Ethylparaben 0.20 Propylparaben 0.20 Triethanolamine 0.20 100.00

We also found that the following ingredients are most contusive tomixing by use of a cold process when producing a topical solution usingthe present invention where the topical solution is in the form of acream:

Cream Deionized Water 62.6.0 Grape extract 6.00 Isoprene Glycol 5.00Squalane 4.00 Santalum Album Sandalwood Extract 4.00 PhellodendronAmurense Bank Extract, Hordeum Distichon (Barley) Extract,Polyglyceryl-2 Stearate 2.00 Ceteary Methicone (and) Dimethicone 2.00(and) Linleic Acid (and) Glycine Soja (soybean) Sterol (and)Phosopholipids Dimethylopolsiloxane 2.00 Chenesis (Jojoba) Seed Oil 2.00Tetrahexyldecyl Ascrobate 3.00 Tocopheryl Acetate (Vitamin E) 3.00 CetylAlcohol 1.00 Shea Butter 1.00 Phenoxyethanol (and) Methylparaben 1.00(and) Butylparaben (and) Ethylparaben (and) Propylparaben Bees Wax 0.50Cetearyl Glycoside 0.50 Xanthan Gum 0.20 Carbomer 0.2 Total 100.00

It is important a topical lotion have a pH no less than 2.5 and no morethan 8.0. If the pH of the topical solution composition is less than apH of 2.5 or more than a pH of 8.0 the topical solution will burn theskin. The pH level of grape extract is between 1.0 and 2.0 which ifapplied would burn the skin. Therefore additional materials must beadded to increase the pH level. In the present invention a form ofvitamin E for example Tocopherol with a pH level between 4.0 and 7.0 isadded to the topical solution and a form of vitamin B for examplePanthenol with a pH level between 4.0 and 7.0 is added to the topicalsolution to increase the pH level. Either a form of vitamin E, a form ofvitamin B or a form of vitamin E and vitamin B may be used to increasethe level of pH of the grape extract. Furthermore it is well known inthe art that both vitamin E and vitamin B act to moisturize the skinthereby further complimenting the topical solution. Also, vitamin E andvitamin B are compatible with the cold process of the present invention.

The topical solution composition comprises: 0.1% to 50.0% of Grapeextract of the total mixture and 0.100% to 50.0% of an aqueous solutionwith a carbomer base of the total mixture, 0. 1% to 50.0% of Vitamin B5,0. 1% to 50.0% of Vitamin E and, 0.1% to 50.0% water of the totalmixture.

Results of our clinical study where subjects used the topical solutionshowed statistically significant improvements in AK's on skin. Eachstudy subject was his/her own control. One side of the face was treatedwith the topical solution, while the other side was treated with aplacebo gel which was simply the vehicle of the first topical gelwithout the skin lotion. The results show approximately 50%-85%improvement of AK's on the treatment side while the placebo side showlittle improvement or even progression of AK's. For example, in FIG. 1 ,the subject's treated side prior to treatment show 5 AK lesions andpost-treatment show only 3 AK's. In FIG. 2 , the treatment side of thissubject showed 5 AK lesions and post-treatment shows only 1 AK lesion.These results were based on gross visual exam by the researchinvestigator whose specialty is dermatology and confirmed by biopsy ofskin lesions of the subjects on both sides of their faces.

The reduction of AK lesions after treatment with the skin lotioneffectively makes it possible to treat a large area of skin affectedwith large number of AK's without significant side effects ordiscontinuation due to discomfort. Also, because our product has a lowside effect profile, it can be used as a long-tern maintenance productfor patients with sun damaged skin to treat any subclinical cellularatypia that may not have been detected yet.

During the fermentation process resveratrol is produced from aCourraroyl CoA molecule with three Coumaroyl CoA molecules in threesuccessive reduction reactions yielding a long chain molecule calledtetraketide with a single benzene ring. Then that molecule is furtherprocess in acyclization process by either the resveratrol synthase orchalcone synthase to yield the final product of resveratrol or quercitinrespectively. Our experience with various forms of red wine from avariety of grapes, and length of fermentation has resulted in a productthat contains the highest quality of grape extract.

Various embodiments of the invention have been described. These andother embodiments are within the scope of the following claims.

Red Wine Composition for Inhibition of Pigmented Lesions on Human Skin

Certain aspects of the present disclosure include a red wine basedcomposition suitable for use in the inhibition of pigmented lesions onhuman skin, to methods of making such a composition, and the methods ofuse of such a composition. Some such aspect includes a topical solutioncomposition that exhibits the ability to lighten the appearance of humanskin.

Without being bound by theory, it is believed that resveratrol,functioning as an anti-oxidant, has the effect of reducing melanindeposits on the surface of human skin. Resveratrol, a compound withinred wine grape extract, has significant anti-inflammatory andanti-oxidant abilities. As the sole active ingredient, however,resveratrol is typically not directly applied to skin except in verysmall quantities, because resveratrol can cause skin irritation.

Without being bound by theory, it is believed that red wine grapeextract, having a high concentration of resveratrol, has significantbenefits for anti-oxidant activity upon human skin. For example, asdisclosed in U.S. patent application Ser. No. 11/837,735 (the '735application) and U.S. patent application Ser. No. 15/685,687 (the '687application), grapes, fermented in accordance with the fermentationprocedures described therein to develop the strength of the resveratrolwithout damaging its antioxidant abilities, are combined with vitaminsin a carbomer base to create an effective topical composition to restoreUV-radiation damaged skin. The abilities of such formulations wereestablished by testing such formulations on patients with ActinicKeratosis (AK), a precursor condition to Squamous Cell Carcinoma (SCC)where lesions are visible on affected skin. The red wine-based topicalsolutions of such formulations exhibited the ability to reduce theappearance of AKs by an average of at least 75 percent within atwo-month period of application. However, without being bound by theory,application of such formulations of red wine grape extract upon skinwithin a carbomer-based emulsifier does not appear to affecthyperpigmentation in a significant way, despite the relatively highanti-oxidant strength of such formulations. Still, without being boundby theory, it is believed that red wine extract does have the potentialto be effective versus hyperpigmentation and especially PIH(post-inflammatory hyperpigmentation) because of red wine'santi-inflammatory properties.

In some aspects, the topical solution composition exhibits the abilityto reduce the appearance of excessive pigmentation, or“hyperpigmentation”, and to lighten the appearance of human skin. Theproduction of the topical solution is accomplished by providing a grapewine extract (also referred to herein as a grape extract) and addingvitamins that are capable of altering the pH of the topical solutioncomposition within an aqueous solution with a carbomer base. Thecarbomer base acts as an emulsion stabilizer or “emulsifier.”

In some aspects, the use of the topical solution composition disclosedherein reduces the appearance of hyperpigmentation by combining theextract of red wine grapes with one or more vitamins that functionadjust the pH of the topical solution composition to an ideal level formaximum effect, without causing inflammation to the user's skin uponapplication.

Certain aspects of the present disclosure include a base formula ofextract using a high concentration of magenta-colored red wine grapesthat are fermented into wine via a controlled process, as specifiedherein above and in the ‘735 and 687’ applications. Such extract of suchfermented grapes is then combined with one or more vitamins, such asPanthenol (Vitamin B5) and/or Tocopherol Acetate (Vitamin E). In somesuch aspects, the vitamins are combined with the extract within a coldmanufacturing process, in which the extract and vitamins are mixed at atemperature of ranging between 20 degrees Celsius and 40 degrees Celsiusto compound a stable solution that maximizes the effects of a highconcentration of resveratrol within the red wine extract. Panthenol andTocopherol Acetate are used within the solution to adjust the pH levelin order to maintain the solution's anti-oxidant effectiveness andstability.

In certain aspects, the pH of the topical solution composition rangesfrom 2.5 to 5.5, or from 3.0 to 5.0, or from 3.5 to 4.5, for example. Asevidenced below, in Example 1, it has been found that when the pH of thetopical solution composition is from 2.5 to 5.5, the topical solutioncomposition is effective in reducing the visibility of pigmented lesionson skin without causing skin irritation. In some such aspects, thetopical solution composition has a pH of from 2.5 to 5.5 and a contentof red wine grape extract of from 1.0 to 50.0 weight percent. Withoutbeing bound by theory, it is believed that an otherwise identicaltopical solution composition having a pH of greater than 5.5 is noteffective at reducing the visibility of pigmented lesions on skinwithout causing skin irritation, and that an otherwise identical topicalsolution composition having a pH of less than 2.5 causes skinirritation.

In some aspects, a topical solution composition in accordance with thepresent disclosure, having a pH of from 2.5 to 5.5 and a content of redwine grape extract of from 1.0 to 50.0 weight percent, is capable ofreducing the number of visible lesions by from 10% to 50%, or from 15%to 40%, or from 20% to 35%, or from 25% to 30% (e.g., after a twicedaily application of the topical solution composition onto the skin overa thirty-day period). For example, if a user applies the topicalsolution composition to an affected area having ten visible lesions,twice daily for thirty days, that user may experience a reduction in thenumber of visible lesions by from 10% to 50% (i.e., reducing the numberof visible lesions from an original 10 visible lesions to a resultingnumber of visible lesions ranging from 9 to 5). One skilled in the artwould understand that the number of visible lesions reduced by use ofthe present topical solution composition is not limited to thesepercentages.

Without being bound by theory, it is believed that the reduction ofhyperpigmentation results from a combination of the anti-oxidant andanti-inflammatory properties of red wine grape extract and thecomposition having a pH ranging from 2.5 to 5.5. Healthy and normalhuman skin has a pH of approximately 7.0 or neutral pH. However, theouter layers of human skin within the stratum corneum and epidermallayer have a pH level of approximately 5.5 for normal, healthy skin.Thus, by having a pH adjusted to reside within the range of 2.5 to 5.5,the present composition is more effective in reducing lesions ofpigmentation on the upper skin layers, as well as reducing visibleinflammation. That the pH levels maintain a difference in performance isan observation unique to the present composition, as one skilled in theart would have no expectation of success in adjusting the pH level of atopical solution to enhance that solutions abilities to reducehyperpigmentation. In fact, often solutions of known skin lighteners,such as hydroquinone, require functional pHs of 2.0 or lower to bedeemed effective. Thus, the present composition surprisingly andunexpectedly exhibits skin lightening capability at a pH ranging from2.5 to 5.5.

The content of red wine grape extract may range from 1.0 to 50.0 weightpercent, or from 5 to 45 weight percent, or from 10 to 40 weightpercent, or from 15 to 35 weight percent, or from 20 to 30 weightpercent, based on a total weight of the topical solution composition.

The use of the cold manufacturing process described herein, the use of apH range of from 2.5 to 5.5, and the need to stabilize the red wineextract within the emulsion are each considered when determining thetypes and amounts of additives and additional ingredients includedwithin the topical solution composition.

In some aspects, the topical solution composition is in the form of agel. In other aspects, the topical solution composition is in the formof a cream.

Some aspects of the topical solution composition gel includeingredients, including but not limited to: deionized water, red wineextract, Aloe barbendesis leaf juice, cucumber extract, hyaluronic acid,isoprene glycol, tocopherol acetate (Vitamin E), chamomile extract,jojoba oil, hydrolized silk protein, nettle extract, hydrolyzed wheatprotein, phytic acid, wheat germ oil, horsetail extract, Centellaasiatica extract, Chlorella vulgaris extract, hydrolized align, butyleneglycol, D-Panthenol (Vitamin B5), caffeine extract, carbomer,phenoxyethanol, methylparaben, butylparaben, ethylparaben,propylparaben, triethanolamine, or combinations thereof. Some aspects ofthe topical solution composition gel include deionized water in anamount ranging from 51 to 95 weight percent, or from 60 to 90 weightpercent, or from 65 to 85 weight percent, or 70.9 weight percent. Someaspects of the topical solution composition gel include red wine extractin an amount ranging from 1 to 50 weight percent, or from 2 to 20 weightpercent, or from 3 to 10 weight percent, or 5 weight percent. Someaspects of the topical solution composition gel include Aloe barbendesisleaf juice in an amount ranging from 1 to 10 weight percent, or from 2to 8 weight percent, or from 2.5 to 5 weight percent, or 3 weightpercent. Some aspects of the topical solution composition gel includecucumber extract, hyaluronic acid, isoprene glycol, tocopherol acetate(Vitamin E), chamomile extract, jojoba oil, hydrolized silk protein,each, if present, in an amount ranging from 1 to 10 weight percent, orfrom 1.5 to 8 weight percent, or from 2 to 5 weight percent, or 2 weightpercent. Some aspects of the topical solution composition gel includenettle extract, hydrolyzed wheat protein, phytic acid, wheat germ oil,horsetail extract, Centella asiatica extract, Chlorella vulgarisextract, hydrolized align, butylene glycol, D-Panthenol (Vitamin B5),caffeine extract, and carbomer, each, if present, in an amount rangingfrom 0.1 to 5 weight percent, or from 0.2 to 3 weight percent, or from0.3 to 1 weight percent, or 0.5 weight percent. Some aspects of thetopical solution composition gel include phenoxyethanol, methylparaben,butylparaben, ethylparaben, propylparaben, triethanolamine, each, ifpresent, in an amount ranging from 0.01 to 1 weight percent, or from0.02 to 0.5 weight percent, or from 0.09 to 0.3 weight percent, or 0.2weight percent, or 0.1 weight percent. An exemplary gel composition,conducive to mixing via the cold manufacturing process when producingthe topical solution composition, is set forth in the following Table,below.

TABLE Red Wine Gel for reducing hyperpigmentation Red Wine Gel forreducing hyperpigmentation Percentages Ingredients by volume DeionizedWater 70.9 Red Wine Extract 5.0 Aloe Barbendesis Leaf Juice 3.0 CucumberExtract 2.0 Hyaluronic Acid 2.0 Isoprene Glycol 2.0 Tocopherol Acetate(Vitamin E) 2.0 Chamomile Extract 2.0 Jojoba Oil 2.0 Hydrolized SilkProtein 2.0 Nettle Extract 0.5 Hydrolyzed Wheat Protein 0.5 Phytic Acid0.5 Wheat Germ Oil 0.5 Horsetail Extract 0.5 Centella Asiatica Extract0.5 Chlorella Vulgaris Extract 0.5 Hydrolized Algin 0.5 Butylene Glycol0.5 D-Panthenol (Vitamin B5) 0.5 Caffeine Extract 0.5 Carbomer 0.5Phenoxyethanol 0.2 Methylparaben 0.2 Butylparaben 0.2 Ethylparaben 0.2Propylparaben 0.2 Triethanolamine 0.1

Some aspects of the topical solution composition cream includeingredients, including but not limited to: deionized water, red wineextract, isoprene glycol, dimethicone, dimethylpolisiloxane, squalane,chinesis seed oil, tetrahexyldecyl ascorbate (Vitamin C), tocopherolacetate (Vitamin E), panthenol (Vitamin B5), cetyl alcohol, shea butter,bees wax, cetearyl glycoside, xanthan gum, carbomer, Santalum album(sandalwood) extract, Phellondendron amurence bark extract, Hordeiumdistichon (barley) extract, phenoxyethanol, methylparaben,propylparaben, butylparaben, or combinations thereof. Some aspects ofthe topical solution composition cream include deionized water in anamount ranging from 40 to 95 weight percent, or from 50 to 80 weightpercent, or from 55 to 70 weight percent, or 60 weight percent. Someaspects of the topical solution composition cream include red wineextract in an amount ranging from 1 to 50 weight percent, or from 2 to20 weight percent, or from 3 to 10 weight percent, or 6 weight percent.Some aspects of the topical solution composition cream include isopreneglycol, dimethicone, dimethylpolisiloxane, or combinations thereof,each, if present, in an amount ranging from 1 to 10 weight percent, orfrom 1.5 to 8 weight percent, or from 2 to 5 weight percent, or 4 weightpercent or 5 weight percent. Some aspects of the topical solutioncomposition cream include squalane, Chinese seed oil, tetrahexyldecylascorbate (Vitamin C), tocopherol acetate (Vitamin E), panthenol(Vitamin B5), cetyl alcohol, shea butter, bees wax, cetearyl glycoside,xanthan gum, or combinations thereof, each, if present, in an amountranging from 0.1 to 10 weight percent, or from 0.2 to 8 weight percent,or from 0.3 to 5 weight percent, or from 1 to 2 weight percent, or 1weight percent, or 2 weight percent. Some aspects of the topicalsolution composition cream include carbomer, Santalum album (sandalwood)extract, Phellondendron amurence bark extract, Hordeium distichon(barley) extract, phenoxyethanol, methylparaben, propylparaben,butylparaben, or combinations thereof, each, if present, in an amountranging from 0.1 to 5 weight percent, or from 0.2 to 3 weight percent,or from 0.25 to 1 weight percent, or from 0.25 to 0.5 weight percent, or0.5 weight percent, or 0.25 weight percent. An exemplary creamcomposition, conducive to mixing via the cold manufacturing process whenproducing the topical solution composition, is set forth in thefollowing Table, below.

TABLE Red Wine Cream for reducing hyperpigmentation Red Wine Cream forreducing hyperpigmentation Percentages Ingredients by volume DeionizedWater 60.0 Red Wine Extract 6.0 Isoprene Glycol 5.0 Dimethicone 4.0Dimethylpolisiloxane 4.0 Squalane 2.0 Chinesis Seed Oil 2.0Tetrahexyldecyl Ascorbate (Vitamin C) 2.0 Tocopherol Acetate (Vitamin E)2.0 Panthenol (Vitamin B5) 2.0 Cetyl Alcohol 2.0 Shea Butter 2.0 BeesWax 2.0 Cetearyl Glycoside 1.0 Xanthan Gum 1.0 Carbomer 0.5 SantalumAlbum (Sandalwood) Extract 0.5 Phellondendron Amurence Bark Extract 0.5Hordeium Distichon (Barley) Extract 0.5 Phenoxyethanol 0.25Methylparaben 0.25 Propylparaben 0.25 Butylparaben 0.25

As is understood by those skilled in the art, different combinations ofingredients may be used without deviating from the scope of the presentdisclosure.

EXAMPLE 1 Red Wine Lightning Laboratory Trial

A trial experiment was conducted to investigate a red wine gelformulation in accordance the formulation listed in the Table above(TABLE—Red Wine Gel for reducing hyperpigmentation).

Test Materials Used in Example 1

Unit A: Red wine & Vitamin B5 Gel at a 5 weight % concentration; with apH of 5.5

Unit B: Red Wine & B5 Gel at a 5 weight % concentration; with a pH at2.5

Unit C: Control gel consisting of Vitamin B5 but no red wine extract;with a pH at 7.0

Test Subjects

Six patients were included in the study:

#1: 65 year old Asian female

#2: 50 year old Asian female

#3: 50 year old Asian female

#4: 45 year old Caucasian male

#5: 25 year old Hispanic male

#6: 25 year old Asian male

All subjects at the time of the testing were of generally good health.

Study Methodology

The subjects (i.e., six patients) were each given a 30 ml bottle of agel formulation that was marked A, B or C, corresponding to Units A, B,and C. Thus, each bottle corresponded to one of the test materials. Thesubjects were instructed to wash their face and then apply the gel twicedaily: once in the morning and once before going to sleep. The amountapplied to the face was 0.3 grams per dose (per application). The studywas conducted for 30 days.

Results of Study

The study was judged based on the attained reduction of visiblepigmentation lesions by area, by visual assessment from Day 1 of thestudy before the first application of gel, to the Day 30 of the study,after the final application of gel. The results are presented in theTable below.

TABLE Example 1 Study Results Subject Gel Used Result Day 1 Result Day30 1 B — 50% reduction in visible pigmentation lesions 2 B — 45%reduction in visible pigmentation lesions 3 A — 10% reduction in visiblepigmentation lesions 4 C — 0% reduction in visible pigmentation lesions5 C — 3% reduction in visible pigmentation lesions 6 A — 18% reductionin visible pigmentation lesions

The percentage in the Table is the amount of area of pigmented lesionsreduced on the face. This was done as a self-assessment by the subject,and also by an observer to determine the amount of reduced lesions.

Conclusions

This study was able to observe that there was a noticeably visibleresult from application of gels with Red Wine Extract on reducingpigmented lesions, and that this result was especially apparent on gelswith a lower pH than 7.0. Compared to the control gel, both of the redwine gels were able to display visible results.

It was found however that when the pH of the gel was narrowed to between2.5 and 5.5, and not exceeding 5.5, and when the concentrations of thered wine extract were between 1.0% and 50.0%, that the resulting gel wasobserved as being effective in reducing the visibility of pigmentedlesions on skin that it was applied to. Topical solutions employing redwine extract that had a pH above 5.5 were found not to be effective inreducing hyperpigmented lesions on skin, while solutions that were below2.5 were found to be highly inflammatory on skin to the point ofineffectiveness.

It should be noted and understood that many of the specific features orcombination of features illustrated in or introduced above (or describedin the claims submitted below), and\or discussed in accompanyingdescriptions, may be combined with or incorporated with or otherfeature(s) described or illustrated in any other Figure provided herein.Moreover, the following claims serve also to describe and illustratesome (but not all) aspects of the present disclosure. The claims servetherefore as an integral part of the present disclosure.

The foregoing description has been presented for purposes ofillustration and description of preferred aspects. This description isnot intended to limit associated concepts to the various compositions,processes, and methods specifically described herein. For example,aspects of the processes and compositions illustrated by the Figures anddiscussed above may be employed or prove suitable for use with methodsand compositions. The aspects described and illustrated herein arefurther intended to explain the best modes for practicing thecompositions and methods, and to enable others skilled in the art toutilize same and other aspects and with various modifications requiredby the particular applications or uses of the present disclosure.

1-37. (canceled)
 38. A topical solution composition comprising: a redwine extract present in an amount ranging from 1.0 to 50.0 weightpercent based on a total weight of the topical solution composition, thered wine extract comprising resveratrol; water; and vitamins, whereinthe vitamins are present in the topical solution composition in anamount that is sufficient to provide the topical solution compositionwith a pH ranging from 2.5 to 5.5.
 39. The topical solution compositionof claim 38, wherein the topical solution composition exhibits thecapability of reducing the number of visible lesions on human skin. 40.The topical solution composition of claim 38, wherein the resveratrolcomprises cis- and trans-resveratrol.
 41. The topical solutioncomposition of claim 38, further comprising an emulsifier.
 42. Thetopical solution composition of claim 41, wherein the emulsifiercomprises a carbomer base.
 43. The topical solution composition of claim38, wherein the red wine extract is an extract of fermented grapeshaving concentrations of resveratrol.
 44. The topical solutioncomposition of claim 43, wherein the red wine extract has an amount ofalcohol of no more than 2 percent by volume.
 45. The topical solutioncomposition of claim 44, wherein the red wine extract is an extract fromgrapes fermented by use of yeast as an agent for a duration of betweenseven days and forty-five days, at a temperature between 35 degrees F.and 95 degrees F., and at a humidity between 30 percent and 80 percent.46. The topical solution composition of claim 38, wherein the red wineextract is extracted from magenta-colored red wine grapes.
 47. Thetopical solution composition of claim 38, wherein the red wine extractis extracted from merlot grapes, cabernet grapes, or combinationsthereof.
 48. The topical solution composition of claim 38, wherein thered wine extract is in powder form.
 49. The topical solution compositionof claim 38, wherein the vitamins comprise vitamin B5, vitamin E, orcombinations thereof.
 50. The topical solution composition of claim 38,wherein the topical solution composition is in the form of the topicalgel.
 51. The topical solution composition of claim 50, wherein thetopical solution composition comprises Aloe barbendesis leaf juice,cucumber extract, hyaluronic acid, isoprene glycol, tocopherol acetate(Vitamin E), chamomile extract, jojoba oil, hydrolyzed silk protein,nettle extract, hydrolyzed wheat protein, phytic acid, wheat germ oil,horsetail extract, Centella asiatica extract, Chlorella vulgarisextract, hydrolyzed align, butylene glycol, D-Panthenol (Vitamin B5),caffeine extract, carbomer, phenoxyethanol, methylparaben, butylparaben,ethylparaben, propylparaben, triethanolamine, or combinations thereof.52. The topical solution composition of claim 50, wherein the topicalsolution composition comprises Carbomer, Isoprene Glycol, Xanthan Gum,Butylene Glycol, or combinations thereof.
 53. The topical solutioncomposition of claim 38, wherein the topical solution composition is inthe form of the topical cream.
 54. The topical solution composition ofclaim 53, wherein the topical solution composition comprises isopreneglycol, dimethicone, dimethylpolysiloxane, squalane, chinesis seed oil,tetrahexyldecyl ascorbate (Vitamin C), tocopherol acetate (Vitamin E),panthenol (Vitamin B5), cetyl alcohol, shea butter, bees wax, cetearylglycoside, xanthan gum, carbomer, Santalum album (sandalwood) extract,Phellodendron amurense bark extract, Hordeum distichon (barley) extract,phenoxyethanol, methylparaben, propylparaben, butylparaben, orcombinations thereof.
 55. The topical solution composition of claim 53,wherein the topical solution composition comprises Isoprene Glycol,Polyglyceryl-2 Stearate, Dimethylpolysiloxane Cetyl Alcohol, Bees Wax,Cetearyl Glucoside, Xanthan Gum, Carbomer, or combinations thereof. 56.A topical solution composition comprising: a red wine extract present inan amount ranging from 1.0 to 50.0 weight percent based on a totalweight of the topical solution composition, the red wine extractcomprising resveratrol; water; an emulsifier; vitamins, wherein thevitamins are present in the topical solution composition in an amountthat is sufficient to provide the topical solution composition with a pHranging from 2.5 to 5.5; wherein the topical solution composition is inthe form of a topical gel or a topical cream; and wherein the topicalsolution composition exhibits the capability of reducing the number ofvisible lesions on human skin.
 57. A topical solution compositioncomprising: a red wine extract present in an amount ranging from 1.0 to50.0 weight percent based on a total weight of the topical solutioncomposition, the red wine extract comprising resveratrol; water; anemulsifier; vitamins, wherein the vitamins are present in the topicalsolution composition in an amount that is sufficient to provide thetopical solution composition with a pH ranging from 2.5 to 5.5; whereinthe topical solution composition exhibits the capability of reducing thenumber of visible lesions on human skin.